The objective of the Specialized Cooperative Centers Program in Reproduction Research (SCCPRR) at the University of Maryland Medical Center is to conduct innovative basic and clinical research in the reproductive sciences and to apply the knowledge gained from these studies to improve understanding of the etiology and treatment of infertility in women. A multidisciplinary experimental approach will be taken in this program to study function of the pituitary-ovarian- uterine axis as related to the central theme on cellular remodeling. In Project I (Karen A. Gregerson, PI), the physiological importance of an inwardly-rectifying, dopamine-activated pituitary K+ channel to prolactin secretion and fertility will be determined in transgenic mice in which the function of this novel membrane channel is interrupted by dominant-negative mutation. In Project II (Gerald J. Pepe, PI), the regulatory role of estrogen on fetal ovarian follicular and oocyte development and the impact on fertility will be assessed in baboons in which placental estrogen synthesis is suppressed in utero by administration of a novel aromatase inhibitor. In Project III (Robert D. Koos, PI), the physiological role of members of the fibroblast growth factor family, bFGF and keratinocyte growth factor, on ovarian and uterine function and fertility will be studied in transgenic mice in which the truncated, dominant-negative FGF receptors are spatially and temporally overexpressed. A combined clinical-basic research study is proposed in Project IV (Eugene D. Albrecht, PI), in which the roles of estrogen and progesterone, acting via vascular endothelial growth/ permeability factor and bFGF, on endometrial angiogenesis and fertility will be investigated in vivo in baboons and in vitro in the human endometrium. Each of the research projects will draw heavily upon the Cell Immunocytochemistry/In Situ Hybridization Core (Gloria E. Hoffman, PI) for the cellular localization of regulatory peptides and steroid hormone receptors. Integration of the scientific effort in this SCCPRR will be achieved through the thematic focus on cellular remodeling, common technological molecular approaches, and an established tradition of collaborative research.